Light-based therapies for cancer: Reshaping the tumor microenvironment and antitumor immunity

Light-based therapeutic modalities, including photoimmunotherapy (PIT), photodynamic therapy (PDT), and light-responsive nanomedicine, have emerged as powerful localized approaches for targeted cancer treatment. Beyond their direct cytotoxic and antivascular effects, these therapies uniquely induce immunogenic cell death (ICD), leading to the rapid release of damage-associated molecular patterns (DAMPs) and tumor antigens. This immunogenic cascade promotes dendritic cell maturation and enhances systemic antitumor immune responses. Crucially, light-based interventions possess the unique ability to physically and biologically remodel the immunosuppressive tumor microenvironment (TME) by disrupting dense extracellular matrices, relieving hypoxia, and modulating local immune cell populations. Understanding how light-triggered therapies modulate complex TME dynamics is essential for overcoming current resistance mechanisms in cancer immunotherapy and developing more effective, durable systemic therapeutic strategies.Despite significant technological and translational advancements, major challenges remain in optimizing light-based cancer therapies. These include overcoming limited tissue penetration of light, addressing heterogeneous TME immunosuppression, and maximizing systemic immune memory to prevent local recurrence and distant metastasis. Recent developments in advanced photo-nanomedicine, highly specific cell-targeting molecular conjugates, and novel combination regimens, such as integrating light therapies with immune checkpoint inhibitors or cellular immunotherapies, offer unprecedented opportunities to address these challenges.This Research Topic aims to collect cutting-edge original research, comprehensive reviews, and translational perspectives focused on light-based modalities and their interplay with cancer immunity. We particularly welcome contributions addressing mechanistic insights into light-induced immunogenic cell death and immune cell activation, physical and biological remodeling of the immunosuppressive TME, novel light-driven nanomedicines and drug delivery platforms, synergistic combinations of phototherapies with systemic immunotherapies and targeted agents, and translational and clinical progress in photoimmunotherapy and photodynamic therapy.We welcome Original Research, Reviews, Mini Reviews, Methods, and Perspective articles that advance our understanding of light-based therapies and their impact on tumor microenvironment dynamics and systemic cancer immunity. We encourage submissions covering, but not limited to, the following themes:- Molecular mechanisms of light-induced immunogenic cell death and downstream immune cell recruitment and activation.- Physical and biological remodeling of the immunosuppressive tumor microenvironment, including matrix disruption, vascular normalization, and stromal modulation.- Advanced photo-nanomedicines, light-responsive drug delivery systems, and theranostic approaches.- Synergistic combinations of phototherapies (photodynamic therapy, photoimmunotherapy, photothermal therapy) with immune checkpoint blockade, adoptive cell therapies, or novel immunomodulators.- Preclinical models and translational or clinical studies investigating systemic immune memory and abscopal effects driven by localized light treatment.Conflict of interest statement: Dr. Juan Luis Santiago declares no competing interests with regard to the Research Topic subject. Topic editors: Takahiro Tsujikawa, Juan Luis Santiago, Ryuhei Okada Source: https://www.frontiersin.org/research-topics/86679/light-based-therapies-for-cancer-reshaping-the-tumor-microenvironment-and-antitumor-immunity